vasoactive-intestinal-peptide and Atrophy

The pathology, aetiology and clinical features of cystic fibrosis (CF) are briefly reviewed. The diffuse endocrine system (DES) may be involved in either a primary or secondary manner. Carbohydrate intolerance is common and the release of islet hormones is deficient, as is the release of the intestinal hormone gastric inhibitory polypeptide (GIP). The post-prandial responses of insulin and GIP can be improved by substituting an elemental meal, suggesting that malabsorption and local intestinal factors could be causative in the deficient responses. Vasoactive intestinal polypeptide-like immunoreactive (VIP-LI) cell numbers are increased in CF and an intimate association with mucous cells is noted suggesting a paracrine relationship. These findings could have implications in the diagnosis, management and aetiology of CF.

Topics: Atrophy; Cystic Fibrosis; Diabetes Mellitus; Endocrine Glands; Food; Gastric Inhibitory Polypeptide; Glucagon; Histocytochemistry; Humans; Insulin; Jejunum; Pancreas; Pancreatic Polypeptide; Vasoactive Intestinal Peptide

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Atrophy; Brain; Female; Mice; Neuroprotective Agents; Vasoactive Intestinal Peptide

Attempts have been made to improve nerve conduits in peripheral nerve reconstruction. We investigated the potential therapeutic effect of a vasoactive intestinal peptide (VIP), a neuropeptide with neuroprotective, trophic and developmental regulatory actions, in peripheral nerve regeneration in a severe model of nerve injury that was repaired with nerve conduits.. The sciatic nerve of each male Wistar rat was transected unilaterally at 10 mm and then repaired with Dl-lactic-ε-caprolactone conduits. The rats were treated locally with saline, with the VIP, with adipose-derived mesenchymal stem cells (ASCs) or with ASCs that were transduced with the VIP-expressing lentivirus. The rats with the transected nerve, with no repairs, were used as untreated controls. At 12 weeks post-surgery, we assessed their limb function by measuring the ankle stance angle and the percentage of their muscle mass reduction, and we evaluated the histopathology, immunohistochemistry and morphometry of the myelinated fibers.. The rats that received a single injection of VIP-expressing ASCs showed a significant functional recovery in the ankle stance angle (p = 0.049) and a higher number of myelinated fibers in the middle and distal segments of the operated nerve versus the other groups (p = 0.046).. These results suggest that utilization of a cellular substrate, plus a VIP source, is a promising method for enhancing nerve regeneration using Dl-lactic-ε-caprolactone conduits and that this method represents a potential useful clinical approach to repairing peripheral nerve damage.

Topics: Adipose Tissue; Animals; Atrophy; Biocompatible Materials; Caproates; Gene Transfer Techniques; Lactones; Lentivirus; Male; Mesenchymal Stem Cell Transplantation; Mice; Mice, Inbred BALB C; Muscle, Skeletal; Peripheral Nerves; Rats; Rats, Wistar; Vasoactive Intestinal Peptide

Toxoplasma gondii (T. gondii) crosses the intestinal barrier in oral infections and can lead to changes in different cell types, including the neurons located there. In the gastrointestinal system, the autonomous nervous system component that regulate blood flow and mucous secretion is the submucosal plexus. The aim of this study was to examine the effects of T. gondii infection on intraepithelial lymphocytes (IELs), goblet cells and submucosal neurons that are immunoreactive to vasoactive intestinal peptide (VIP-IR) of rat jejunum. Twenty male rats distributed as a control group (CG) and an infected group (IG), which received a suspension with 500 parasite oocysts (strain ME-49, genotype II) orally, were assessed. Routine histological sections were used to quantify IELs and to detect mucins secreted by goblet cells. Whole mounts including the submucosal layer were examined using immunofluorescence to detect the VIP neurotransmitter. Quantitative alterations in IELs were not observed. However, the reduction (P < 0.05) in the number of goblet cells that produce neutral mucins (PAS+) and sulphomucins (AB pH 1.0) and the maintenance of sialomucin-secreting cells (AB pH 2.5) resulting in a more fluid mucous were observed. Concerning the VIP-IR submucosal neurons, an increase in fluorescence on IG animals was observed. There was a reduction (P < 0.05) in the number of VIP-IR submucosal neurons and atrophy of their cell bodies in IG rats. Infection with T. gondii caused alterations in the chemical composition of the intestinal mucous and reduction in the neuron number and atrophy of the remaining neurons in this cell subpopulation.

Topics: Animals; Atrophy; Cell Count; Disease Models, Animal; Goblet Cells; Jejunum; Lymphocytes; Male; Mucins; Neurons; Rats; Rats, Wistar; Submucous Plexus; Toxoplasma; Toxoplasmosis; Vasoactive Intestinal Peptide

Neurturin, a member of the glial cell-derived neurotrophic factor familys of ligands, is important for development of many cranial parasympathetic ganglion neurons. We have investigated the sacral component of the parasympathetic nervous system in mice with gene deletions for neurturin or its preferred receptor, GFRalpha2. Disruption of neurturin signalling decreased cholinergic VIP innervation to the mucosa of the reproductive organs, but not to the smooth muscle layers of these organs or to the urinary bladder. Thus, neurturin and its receptor are involved in parasympathetic innervation of a select group of pelvic visceral tissues. In contrast, noradrenergic innervation was not affected by the gene ablations. The epithelium of reproductive organs from knockout animals was atrophied, indicating that cholinergic innervation may be important for the maintenance of normal structure. Cholinergic neurons express GFRalpha2 on their terminals and somata, indicating they can respond to neurotrophic support, and their somata are smaller when neurturin signalling is disrupted. Colocalisation studies showed that many peripheral glia express GFRalpha2 although its role in these cells is yet to be determined. Our results indicate that neurturin, acting through GFRalpha2, is essential for parasympathetic innervation of the mucosae of reproductive organs, as well as for maintenance of a broader group of sacral parasympathetic neurons.

Topics: Acetylcholine; Animals; Atrophy; Epithelium; Exocrine Glands; Gene Expression Regulation, Developmental; Genitalia; Glial Cell Line-Derived Neurotrophic Factor Receptors; Male; Mice; Mice, Knockout; Muscle, Smooth; Nerve Growth Factors; Neuroglia; Neurturin; Parasympathetic Nervous System; Presynaptic Terminals; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-ret; Rats; Rats, Wistar; Receptor Protein-Tyrosine Kinases; Sacrum; Signal Transduction; Urinary Bladder; Vasoactive Intestinal Peptide; Viscera

The histopathology of Fibrocalculous Pancreatic Diabetes (FCPD) has been extensively studied, but there are no reports on alteration in patterns of hormone secreting cells using immunohistochemistry in islets of FCPD patients. In this study, we report on the histopathology and immunohistochemistry of islets of FCPD patients and its possible correlation with the clinical picture. Pancreatic biopsies were carried out in six patients with FCPD at the time of surgery for abdominal pain. Routine histopathology and immunohistochemistry studies were carried out with six primary antibodies namely insulin, glucagon, pancreatic polypeptide (PP), somatostatin, vasoactive intestinal peptide and gastrin. Histopathology of the pancreas showed a spectrum of changes ranging from moderate to severe atrophy, fibrosis of the parenchyma and degeneration of the ducts. Nesidioblastosis was present in three patients. Immunohistochemical studies showed a decrease in the number of islets but some patients showed evidence of hyperplasia. There was an overall decrease in the percent of insulin cells and the positivity in the islets correlated with plasma C-peptide levels and the duration of diabetes. There was no consistent relationship with glucagon with some patients showing increased and other decreased positivity. There was a marked decrease in PP and somatostatin positivity, the significance of which is not clear. The reduction, but partial preservation of insulin positivity is consistent with the ketosis resistance shown by patients with Fibrocalculous Pancreatic Diabetes.

Topics: Adolescent; Adult; Atrophy; Biopsy; Blood Glucose; Chronic Disease; Diabetes Mellitus; Female; Gastrins; Glucagon; Humans; Hyperplasia; Immunohistochemistry; Insulin; Islets of Langerhans; Male; Middle Aged; Pancreas; Pancreatic Ducts; Pancreatic Polypeptide; Pancreatitis; Vasoactive Intestinal Peptide

Intestinal inactivity leads to atrophic changes and concomitant alterations in the expression of neurotransmitters in the enteric nervous system. In atrophic rat ileum neurones expressing vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) decrease in number while nitric oxide synthase (NOS) expressing neurones increase. Since little is known about functional changes accompanying intestinal atrophy the aim of the present study was to investigate relaxatory responses to VIP, PACAP-27 and nitric oxide (NO) in longitudinal smooth muscle from atrophic rat ileum.. To create a dysfunctional (atrophic) intestine, the distal 10 cm of rat ileum was surgically bypassed. In vitro experiments were carried out on longitudinal muscle strips from rat ileum having been sham-operated, one week or four weeks bypassed.. The amplitudes of the relaxatory responses to PACAP-27, VIP and the NO-donor S-nitroso-N-acetylpenicillamine (SNAP), but not forskolin, were significantly increased in the one-week bypassed ileum. In the four-weeks bypassed ileum the VIP, PACAP-27, SNAP and forskolin evoked relaxations were of the same magnitude as those of the sham-operated. The augmented responses to both VIP and PACAP-27 could be blocked by pre-treatment with apamin while N(G)-nitro-L-arginine methyl ester (L-NAME) and tetrodotoxin were ineffective. In contrast to sham-operated and four-weeks bypassed ileum, cross-desensitization between VIP and PACAP-27 was noted after one week of bypass.. Intestinal adaptation after bypassing the distal ileum of the rat includes a transient supersensitivity of the longitudinal muscle to the NO donor SNAP, VIP and PACAP-27. These augmented relaxatory responses may contribute to the hypomotility noted in inactive intestine.

Topics: Adaptation, Physiological; Animals; Atrophy; Culture Techniques; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Gastrointestinal Motility; Ileum; Neuropeptides; Nitric Oxide; Pituitary Adenylate Cyclase-Activating Polypeptide; Rats; Rats, Sprague-Dawley; Reference Values; Sensitivity and Specificity; Vasoactive Intestinal Peptide

Inactivity of the gut leads to atrophic changes of which little is known.. To investigate structural, neuronal, and functional changes occurring in bypassed rat ileum.. Morphometry was used to characterise the atrophic changes. The numbers of enteric neurones, their expression of neurotransmitters, and the presence of interstitial cells of Cajal were studied using immunocytochemistry and in situ hybridisation. Motor activity was studied in vitro.. Adaptive changes in bypassed ileum include atrophy and remodelling of the gut wall. The total numbers of submucous and myenteric neurones per unit length increased one and four weeks after bypass but were identical to sham operated intestine 10 weeks after bypass. Neurones expressing vasoactive intestinal peptide, neuropeptide Y, or pituitary adenylate cyclase activating peptide decreased gradually in number in bypassed ileum. Nitric oxide synthase expressing neurones were increased, particularly in the myenteric ganglia. No change in the frequency and distribution of interstitial cells of Cajal was noted. The contractile response elicited by electrical stimulation of sham operated ileum consisted of a fast cholinergic twitch followed by a slower non-adrenergic, non-cholinergic contraction. In the bypassed ileum an identical biphasic contraction was elicited; however, the entire response was non-adrenergic, non-cholinergic. The relaxatory response to electrical stimulation in sham operated ileum was nitric oxide mediated; after bypass it was non-nitrergic.. Notable atrophic changes were seen in the rat ileum after bypass. The enteric nervous system reacted with neuronal cell death and plasticity in terms of release and expression of neurotransmitters.

Topics: Anastomosis, Surgical; Animals; Atrophy; Autoradiography; Calcitonin Gene-Related Peptide; Female; Ileum; In Situ Hybridization; Myenteric Plexus; Neurons; Neuropeptide Y; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Rats; Rats, Sprague-Dawley; RNA, Messenger; Substance P; Vasoactive Intestinal Peptide

The possibility that long-term ethanol ingestion might alter either vasoactive intestinal peptide (VIP) content, VIP binding to membrane receptors, G-protein levels or adenylate cyclase activity in rat prostate was tested, as ethanol produces serious alterations in the hypothalamic-pituitary-gonadal axis and several modifications on different elements on signal transduction pathways in other systems.. Prostatic membranes from control and ethanol-treated (for 4 weeks) rats were used to study adenylate cyclase stimulation as well as for the immunodetection of stimulatory (alpha(s)) and inhibitory (alpha(i)1-2) G-protein subunits. Studies on VIP binding and cross-linking to receptors were performed using [125I]VIP. Prostatic VIP content was estimated by radioimmunoassay. GTPase activity was quantified by measuring the amount of 32Pi released from [gamma-32P]GTP.. Chronic ethanol ingestion resulted in an increased presence of VIP in the rat prostate without any change on the VIP receptor/effector system in this gland. By contrast, the basal adenylate cyclase activity as well as the dose-dependent stimulation of this enzyme by either the nonhydrolyzable GTP analogue Gpp(NH)p or the beta-adrenergic agonist isoproterenol were enhanced in prostatic membranes after ethanol intake. Moreover, an increase in the content of G-protein subunits (alpha(S) and alpha(i)1-2) was observed without any change in GTPase activity in this condition. These modifications were accompanied by a significant decrease in rat prostate weight and, consequently, the height of the secretory epithelium in this gland.. Considering the role of VIP in the mechanisms of secretion and cell proliferation in the prostate, the observed increases in the prostatic content of VIP and G-protein subunits make conceivable that VIP and cAMP signal transduction could be involved in the atrophy of the rat prostate and in the alterations in the composition of seminal fluid that appear in the alcoholic syndrome.

Topics: Adenylyl Cyclases; Alcoholism; Animals; Atrophy; Colforsin; Cyclic AMP; Enzyme Activation; Ethanol; GTP Phosphohydrolases; GTP-Binding Proteins; Guanylyl Imidodiphosphate; In Vitro Techniques; Male; Prostate; Protein Conformation; Rats; Rats, Wistar; Receptors, Vasoactive Intestinal Peptide; Signal Transduction; Vasoactive Intestinal Peptide

Rats were fed a liquid diet with the aim of decreasing nervous reflex activity in the parotid glands. In rats killed after 21 days on this diet the glands were atrophied and the total amounts of the neuropeptides, substance P, vasoactive intestinal peptide and calcitonin gene-related peptide, were lower than in control glands.

Topics: Animals; Atrophy; Calcitonin Gene-Related Peptide; Diet; Female; Organ Size; Parotid Gland; Rats; Rats, Inbred Strains; Sublingual Gland; Submandibular Gland; Substance P; Vasoactive Intestinal Peptide

1. The long-term influence of substance P (SP) and vasoactive intestinal peptide (VIP) on rat salivary gland weight was investigated after parasympathetic denervation or on feeding soft food. 2. The parotid gland lost about one-third of its weight within 4-5 days following parasympathetic post-ganglionic denervation or change in dietary regimen, from pellets to liquid diet, thought to reduce nerve reflex activity. 3. Daily i.v. infusions with SP or VIP diminished or largely prevented the fall in parotid gland weight, whereas infusions with pentagastrin, bethanechol and saline had no effect. The infusions were preceded by administration of alpha- and beta-adrenoceptor antagonists; these antagonists were also given to the control animals. 4. The effect of SP and VIP on the parotid gland weight appeared to be related to cell size rather than to cell number, as judged by measurements of RNA and DNA. 5. Observations on the two other major salivary glands underlined the fact that different gland types in the same animal behave differently. Parasympathetic preganglionic denervation (decentralization) lowered the weights of the sublingual and submandibular glands, whereas liquid diet only reduced the weight of the sublingual gland. SP and VIP did not affect the weights of the submandibular glands, but VIP prevented the slight fall in sublingual gland weight induced by liquid diet. 6. The present results suggest a trophic role in rats for SP and VIP on parotid glands and for VIP on sublingual glands. Such an influence may be exerted naturally as a result of their release from nerves containing these peptides around acini.

Topics: Animals; Atrophy; Blood Pressure; Denervation; Diet; Female; Organ Size; Pancreas; Parasympathetic Nervous System; Rats; Rats, Inbred Strains; Reflex; Salivary Glands; Salivation; Sublingual Gland; Submandibular Gland; Substance P; Sympatholytics; Vasoactive Intestinal Peptide

Immunoreactivity to material like vasoactive intestinal polypeptide was found to occur within certain cellular elements of the epidermis in two patients out of four who had lesions of lichen sclerosus et atrophicus. No specific immunofluorescence to the material could be seen in the dermis, apart from single immunoreactive nerve fibers.

Topics: Adolescent; Adult; Animals; Atrophy; Female; Fluorescent Antibody Technique; Humans; Male; Middle Aged; Peptides; Rabbits; Rats; Sclerosis; Skin; Skin Diseases; Vasoactive Intestinal Peptide

Atrophy of the exocrine pancreas was induced in rats by feeding a copper-deficient diet combined with penicillamine. The treatment resulted in significant decreases in the weights of pancreas and stomach but an increase in the weight of the small intestine compared with control animals receiving the same amount of food. Despite almost total destruction of acinar cells, the content of vasoactive intestinal polypeptide, (VIP) and substance P in the pancreas was not different from controls but the total somatostatin increased by 258% and the glucagon content by 370%. Significant decreases (p less than 0.05) in the concentrations (pmol/g) of VIP, substance P and somatostatin in the small intestine were observed but the total amount (pmol/organ) of the peptides was unchanged. Similarly, an increase (59%) in the concentration of gastric somatostatin in exocrine atrophy was not reflected in a significant difference in the total amount. The content of enteroglucagon in the small intestine was not different in the two groups suggesting that this material was not the trophic influence leading to increased intestinal weight.

Topics: Animals; Atrophy; Copper; Digestive System; Duodenum; Gastric Mucosa; Glucagon; Ileum; Jejunum; Male; Pancreas; Penicillamine; Rats; Rats, Inbred Strains; Somatostatin; Substance P; Vasoactive Intestinal Peptide

Topics: Adult; Aged; Atrophy; Brain Diseases; Female; Gastrointestinal Hormones; Humans; Intervertebral Disc Displacement; Male; Middle Aged; Multiple Sclerosis; Spondylitis; Vasoactive Intestinal Peptide